tbuckley/cabot-search huggingface dataset:
Creatinine to cystatin C ratio and mortality in renal cell carcinoma.
Authors: Benjamin Schmeusser, Adil Ali, Dattatraya H Patil, Eric Midenberg, Reza Nabavizadeh, Kenneth Ogan, Viraj A. Master
Journal: Journal of Clinical Oncology (2023)

697 Background: Creatinine and cystatin C are routinely used to assess renal function. Given creatinine originates from skeletal muscle and cystatin C is produced by nucleated cells, a creatinine to cystatin C ratio (Cr/Cys-C) may positively correlate with muscle mass. Low Cr/Cys-C has also been associated with decreased overall survival (OS) in cancer, including in a combined cohort of genitourinary malignancies. Furthermore, elevated cystatin c has been associated with shorter OS and recurrence free survival (RFS) in renal cell carcinoma (RCC). Cr/Cys-C may be a simple and affordable tool to assist with patient-specific risk stratification. We assess the ability of Cr/Cys-C to predict OS and RFS in patients with RCC. Methods: Retrospective review of a prospectively maintained database identified patients that underwent partial or radical nephrectomy for RCC from 2018-2021. Included patients had preoperative creatinine and cystatin C and 1+ year of follow up. Cr/Cys-C associations with patient/tumor characteristics were determined by generalized chi-square or Fisher’s exact tests for categorical variables and Wilcoxon rank-sum test for continuous variables. Cr/Cys-C ability to predict OS and RFS was analyzed with Kaplan-Meier method and Cox hazards models. Statistical tests were two-sided with type I error set at 0.05. Results: 219 patients were identified. Median age was 64, with most being male (67%). 62% and 29% of patients were white and black, respectively. Median eGFR was 72mL/min/1.73m2. Median (IQR) Cr/Cys-C was 1 (0.8-1.2). 55% were stage T3-T4, with 12% N1 and 16% M1 at time of surgery. 72% had clear cell histology. Low Cr/Cys-C was significantly associated with older age, males, Eastern Cooperative Oncology Group score ≥ 1, radical nephrectomy, T3-T4 stage, and metastasis. Kaplan-Meier curves showed low Cr/Cys-C association with decreased OS (p=0.0003) and RFS (p=0.0094). Cox regression analysis revealed lower Cr/Cys-C as independent predictor of decreased OS (binary HR=3.66, 95% CI 1.2-11.3, p=0.02; continuous HR=0.05, 95% 0.0-0.8, p=0.03) and RFS (binary HR=4.8, 95% CI 1.6-14.6, p=0.006; continuous HR=0.02, 95% 0.0-0.3, p=0.006;Table). Conclusions: Lower Cr/Cys-C may be associated with decreased OS and RFS in patients with RCC. [Table: see text]
Multi-center, retrospective study of first-line systemic therapy ± immune checkpoint inhibition for metastatic neuroendocrine carcinoma of the urinary tract.
Authors: Katharine A. Collier, Nicholas I. Simon, Amy K Taylor, Gregory Hemenway, Tracy L Rose, Corbin Jeffrey Eule, Nishita Tripathi, Christopher Rodman, Uttam Kalluri, Muhammad Zain Farooq, Rana R. McKay, Rohit K. Jain, Guru P. Sonpavde, Randy F. Sweis, Neeraj Agarwal, Elaine T. Lam, Matthew R. Zibelman, Hamid Emamekhoo, Andrea B. Apolo, Amir Mortazavi
Journal: Journal of Clinical Oncology (2023)

467 Background: Neuroendocrine, small cell, or large cell carcinoma originating from the urothelium (uro-NE/SCC/LCC) is rare. Outcomes for metastatic disease are dismal. Treatment is extrapolated from small cell lung cancer, for which immune checkpoint inhibitors (ICIs) have modest activity. Preliminary activity has been reported with ICI for uro-NE. We aimed to compare real-world progression-free survival (PFS) and overall survival (OS) between ICI-containing and non-ICI-containing regimens in the first line (1L) metastatic setting for uro-NE/SCC/LCC. Methods: We performed a retrospective study at 11 cancer centers. Patients (pts) who received systemic therapy (2011-2021) for biopsy confirmed metastatic uro-NE/SCC/LCC were included. Pts with metastasis within 6 months of (neo)adjuvant chemotherapy (CT) (n=16) were excluded from 1L analyses. Results: 102 pts with metastatic uro-NE/SCC/LCC were evaluable. 17 (16.7%) had NE histology, 81 (79.4%) SCC, and 4 (3.9%) LCC. NE/SCC/LCC was mixed with urothelial histology in 19 (18.6%). Primary tumors were most often in the bladder (84.3%, n=86), less frequently upper tract (11.8%, n=12) or urethra (3.9%, n=4). 42 pts (41.2%) were previously treated for localized disease, the rest were de novo metastatic (n=60, 58.8%). Pts who received an ICI in any line (n=61) had significantly longer OS (p=0.038) than pts that never received an ICI (n=41). As shown in the table, in the 1L, ICI-containing regimens (n=33) resulted in significantly longer PFS, but not OS or ORR compared to non-ICI regimens (n=53). Subdividing 1L regimens into ICI without CT (n=14), CT without ICI (n=53), or ICI + CT (n=19), both PFS and OS were significantly different with similar ORR. ICI w/o CT had the longest median PFS and OS with an ORR 57.1% comparable to CT regimens. Of 61 pts that received ICI in any line, 14 (23.0%) had an immune-related adverse event of any grade; 11 (18.0%) received steroids. Conclusions: This is the largest ever report of ICI for metastatic uro-NE/SCC/LCC. ICIs were associated with improved outcomes with expected added toxicity. Further prospective investigation of ICI regimens is warranted. [Table: see text]
Prognostic biomarkers and clinical outcomes in neuroendocrine prostate cancer (NEPC).
Authors: Richard Gagnon, Ealia Khosh Kish, Sarah Cook, Kosuke Takemura, Brian Yu Chieh Cheng, Kamiko Bressler, Daniel Yick Chin Heng, Nimira S. Alimohamed, Joseph D. Ruether, Richard M. Lee-Ying, Pinaki Bose, Michael Paul Kolinsky, Catalina Vasquez, Divya Samuel, John D Lewis, Rehan Faridi, Minal Borkar, Adrian S. Fairey, Tarek A. Bismar, Steven M. Yip
Journal: Journal of Clinical Oncology (2023)

209 Background: NEPC includes both pure small cell carcinoma and mixed tumors with varying degrees of adenocarcinoma and neuroendocrine histology. It arises de novo or is treatment associated (TA) post androgen deprivation therapy. Clinical outcome data and prognostic biomarkers are limited and were thus explored. Methods: Patients with high grade prostate cancer and morphologic and/or immunohistochemical (IHC) NEPC features were included in this retrospective multicentre study. Clinical stage, Gleason score, and serum biomarkers were recorded. Kaplan-Meier method and log-rank test calculated and compared overall survival (OS) from time of NEPC diagnosis.Cox proportional hazards regression assessed prognostic impact of serum biomarkers at diagnosis and de novo vs TA status, adjusting for clinical stage and castration resistance. Results: 135 NEPC cases were identified. 124 (92%) were mixed tumors. 56 (41%) arose de novo. 79 (59%) were TA. 77% of those with a Gleason score (N=85/110) were grade group 5. Median PSA pre-NEPC biopsy was 11.6 ng/mL. At NEPC diagnosis, 19 (14%) had localized disease (median OS 123.0 mo); 33 (24%) non-metastatic castrate-sensitive disease (median OS 42.3 mo); 6 (4%) non-metastatic castrate-resistant disease (median OS 14.3 mo); 35 (26%) metastatic castrate-sensitive disease (median OS 17.6 mo); and 42 (31%) metastatic castrate-resistant disease (median OS 9.6 mo). Median OS for those with visceral metastases was 8.6 mo (95% CI 6.0 – 14.6), compared to patients with non-visceral metastases (11.1 mo; 95% CI 13.7 – 21.5) and no metastases (42.3 mo; 95% CI 47 – 89). Anemia (adjusted HR 1.66; 95% CI 1.05 - 2.16, p = 0.031) and NLR &gt;3 (adjusted HR 1.51; 95% CI 1.01 - 2.52, p = 0.045) were associated with increased risk of death. De novo disease, elevated LDH, serum PSA, and Gleason score were not prognostic. Conclusions: This study identifies NEPC clinical outcomes by stage, with survival poorer than expected in pure prostate adenocarcinoma. Anemia and elevated NLR &gt;3 are prognostic biomarkers that may help risk stratify and guide treatment intensification, including platinum-based chemotherapy. Further biomarker characterization of NEPC through IHC-staining pattern and genomic analysis is currently underway by this group.
Survival trends in de novo metastatic prostate cancer: SEER and Veterans Affairs comparison.
Authors: Martin W. Schoen, Lukas Owens, Suhong Luo, Robert Bruce Montgomery, Kristen Marie Sanfilippo, Ruth Douglas Etzioni
Journal: Journal of Clinical Oncology (2023)

28 Background: Advances in treatment for metastatic prostate cancer (mPC) have improved overall survival (OS) in clinical trials for mPC over the last 20 years. It is unclear whether these changes from trials have translated to improvements in survival in the real world. We sought to characterize trends in OS among patients with newly diagnosed mPC in two large national registries. Methods: Patients diagnosed from 2000-2019 were included. Patients from SEER-17 were included if stage at diagnosis was distant. For years prior to 2004, SEER Historic Stage A was used. Patients in the Veterans Affairs Prostate Cancer data core (VA) were included if the SEER summary stage variable was distant in the first record of prostate cancer in VA or oncology registry data for veterans diagnosed after 2018. Results: 55,661 patients were identified in SEER and 14,904 patients were identified in VA. Median age at presentation was 72 years in both datasets, with 16.6% identified as Black in SEER and 28.5% Black in VA. Median OS from 2000-2004 to 2015-2019 in SEER increased from 25 to 31 months, corresponding to a hazard ratio (HR) of 0.82 (p &lt;0.001); median OS in VA increased from 25.8 to 30.9 months, corresponding to a HR of 0.912 (p=0.003). Patients &lt;70 years of age had median OS that increased from 31 to 41 months (HR 0.78, p &lt;0.001) in SEER and 34.4 to 42.2 months (HR 0.87, p=0.003) in VA compared to patients 70+ in SEER (21 to 26 months, HR=0.84, p&lt;0.001) and in VA (21.6 to 25.6 months, HR=0.935, p=0.03). In SEER, black patients had worse survival compared to white patients (HR 1.10, p&lt;0.001). Survival improvement over time in SEER was seen for both black (HR 0.81, p&lt;0.001) and white (HR 0.83, p&lt;0.001) patients. In VA, black patients had better OS compared to white patients (HR 0.96, p=0.0475). Survival improvement over time in VA was seen in black (HR 0.84, p&lt;0.001), but was not significant in white (HR 0.94, p=0.052) patients. Conclusions: This real-world analysis demonstrates that median OS in de novo mPC has improved over the last 20 years, particularly in patients &lt;70 years of age. However, these improvements are less than what has been observed in clinical trials. Black patients had inferior OS in SEER compared to white patients but in the VA black patients had better OS and an improvement in OS over time, potentially reflecting more equal access to care in the VA system. [Table: see text]
Real-world treatment patterns and progression-free survival among patients with metastatic castration-resistant prostate cancer: Examining the benefits of sequential androgen receptor pathway inhibitor use.
Authors: Jeetvan Patel, Amrita Sawhney, Clare Byrne, Jackson Tang, Channing Yu
Journal: Journal of Clinical Oncology (2023)

64 Background: Numerous treatments with different mechanisms of action are approved for metastatic castration-resistant prostate cancer (mCRPC), but real-world studies increasingly indicate that androgen receptor pathway inhibitors (ARPIs) are the most common treatment choice at both first- (1L) and second-line (2L). Nonetheless, robust evidence on the clinical effectiveness of ARPIs when used sequentially is lacking. The aim of this study was to examine the real-world treatment patterns and associated progression-free survival (PFS) among patients with mCRPC in the United States (US). Methods: This retrospective cohort study used Flatiron Health electronic health record data from 01/01/2013 to 06/30/2020. Included patients were male, aged ≥18 years, had a confirmed diagnosis of mCRPC within the study period, and received ≥1 systemic therapy post-mCRPC diagnosis. Three treatment subgroups were examined, with ARPI defined as abiraterone or enzalutamide: all 1L ARPI users; all 2L ARPI users irrespective of 1L therapy; and 1L ARPI users who received another ARPI at 2L. Treatment patterns were evaluated descriptively; time to next therapy (TTNT) was measured from the start of the ARPI of interest to the start of the subsequent line of therapy. The Kaplan-Meier method was used to evaluate PFS from the start of the ARPI therapy of interest until progression or death from any cause. Results: The study included 2,588 patients (mean age 72 years). ARPIs were the most prescribed systemic therapy in both the 1L and 2L settings: 63% (1,634/2,588) and 46% (808/1,760), respectively. Among 1L ARPI patients, 28.9% received 2L ARPI, 14.0% 2L taxane, 14.3% 2L combo therapies, and 32% received no further therapy. The median TTNT was 7.6, 6.2, and 5.1 months for 1L ARPIs, 2L ARPIs among all users, and 2L ARPIs among patients who received 1L ARPIs, respectively. The corresponding median PFS was 6.5 months, 4.5 months, and 3.9 months, respectively. Conclusions: Among real-world mCRPC patients in the US, ARPIs remain the most common therapy at both 1L and 2L. However, sequential ARPI use appeared to provide diminishing returns, with a PFS of &lt;4 months seen at 2L in those who had received 1L ARPIs. [Table: see text]
Immunohistochemical (IHC) subtypes of metastatic bladder cancer (mBC) using GATA3 and CK5/6.
Authors: Ariel Ann Nelson, Mariel Molina Nunez, Kathryn A. Bylow, Aniko Szabo, Kenneth Iczkowski, Deepak Kilari
Journal: Journal of Clinical Oncology (2023)

557 Background: Genomic analyses have identified that bladder cancers can be divided into distinct molecular subtypes: luminal and basal. IHC markers GATA3 and CK5/6 have demonstrated &gt;80% accuracy in assessing the luminal and basal subtypes of primary bladder tumors and may be easily utilized in clinical practice. Correlation of the primary bladder subtype with that of metastatic sites has not been demonstrated and associations with clinical outcomes are uncertain. Methods: We retrospectively identified patients with mBC who were treated with systemic therapy and had biopsies of either primary bladder or metastatic sites. Patient demographic, metastatic sites, treatment patterns, and clinical outcomes were recorded. Tissue microarrays (TMA) were constructed from primary and/or metastatic tumors. IHC was performed using mouse monoclonal antibodies: GATA-3 (L50-823, Pharmingen, 1:200) and cytokeratin 5/6 (XM26, Thermo Fisher, 1:100). Luminal (GATA3+, CK5/6-), basal (GATA3-, CK5/6+), double positive (GATA3+, CK5/6+) or double negative (GATA3-, CK5/6-) subtyping was applied. Concordance of matched bladder and metastatic pairs was quantified using Cohen’s kappa. Wilcoxon rank-sum tests were used for comparison of continuous and ordinal measures and chi-square tests were performed for comparison of categorical measures. Survival was estimated by Kaplan-Meier method; multivariable Cox analysis was performed. Results: Of 62 specimens, 37 bladder and 16 metastatic sites were interpretable. Four IHC subtype patterns were identified, most were luminal (n=20) followed by double-positive (n=12), basal (n=5), and double-negative (n=5). Of 10 pairs of matched primary tumor and metastatic sites, there was near-perfect subtype concordance between primary and metastatic tumors (κ=0.84; 95% CI:0.58-1.00). No association between sites of metastatic progression and subtype were identified, nor was there any difference in overall survival between the subtypes (p = 0.70). The basal subtype had numerically worse survival compared to the luminal subtype, HR =0.164 (95% CI: 0.02-1.58, p=0.12). Conclusions: IHC subtyping by GATA3 and CK5/6 is feasible in the clinical setting and showed strong correlation between primary and metastatic sites. A larger analysis is planned to further investigate associations with clinical features and outcomes. [Table: see text]
Phase 3 LITESPARK-022: Pembrolizumab (pembro) plus hypoxia-inducible factor 2α (HIF-2α) inhibitor belzutifan as adjuvant treatment for clear cell renal cell carcinoma (ccRCC).
Authors: Toni K. Choueiri, Jens Bedke, Jose A. Karam, Rana R. McKay, Robert J. Motzer, Sumanta Monty Pal, Cristina Suárez, Robert Uzzo, Hong Liu, Joseph E. Burgents, Manish Sharma, Thomas Powles
Journal: Journal of Clinical Oncology (2023)

TPS748 Background: Treatment with the PD-1 inhibitor pembro produced significant improvement in disease-free survival after surgery for patients (pts) with ccRCC in the phase 3 KEYNOTE-564 trial. Based on these results, pembro was approved by the US Food and Drug Administration and the European Medicines Agency for adjuvant treatment of pts with RCC at increased risk of recurrence following nephrectomy or following nephrectomy and resection of metastatic lesions. Despite advances in the treatment landscape for RCC, more effective adjuvant treatment strategies are needed for pts at risk of recurrence after surgery. HIF-2α is an established oncogenic driver in ccRCC, and promising antitumor activity in advanced ccRCC and von Hippel-Lindau disease–associated RCC has been demonstrated with the HIF-2α inhibitor belzutifan. The multicenter, double-blind, randomized, phase 3 LITESPARK-022 study (NCT05239728) will evaluate the efficacy and safety of pembro plus belzutifan compared with placebo plus pembro as adjuvant treatment following nephrectomy in pts with ccRCC. Methods: Key eligibility criteria include adults with histologically or cytologically confirmed intermediate-high risk, high risk, or M1 with no evidence of disease (NED) RCC with a clear cell component; pts with no prior systemic therapy, nephrectomy, and/or metastasectomy ≤12 weeks before randomization; and pts who are tumor free per computed tomography/magnetic resonance imaging. Approximately 1600 pts will be randomly assigned to receive belzutifan 120 mg orally once daily plus pembro 400 mg intravenously (IV) every 6 weeks (Q6W) for ≤9 administrations (~54 weeks) or oral placebo plus pembro 400 mg IV Q6W for ≤9 administrations (~54 weeks) or until verified disease recurrence by blinded independent central review, start of new anticancer treatment, unacceptable toxicity, or decision to withdraw. Stratification factors are tumor grade (1 or 2 vs 3 or 4) and risk type (intermediate-high risk versus high risk versus M1 NED). Pts will be radiologically evaluated Q12W from randomization through year 2, Q16W in years 3 to 5, and Q24W in years 6 and beyond. Adverse events will be monitored throughout the study and for 30 days following cessation of study treatment (90 days for serious adverse events). The primary end point is disease-free survival. Secondary end points include overall survival, safety, disease recurrence–specific survival, and patient-reported outcomes. Recruitment is underway in Asia, Australia, Europe, North America, and South America. © 2022 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2022 ASCO Annual Meeting. All rights reserved. Clinical trial information: NCT05239728 .
Validating the Palacios’ future glomerular filtration rate equation with and without race.
Authors: Benjamin Schmeusser, Adil Ali, Dattatraya H Patil, Arnold Raul Palacios, Manuel Armas-Phan, Kenneth Ogan, Viraj A. Master
Journal: Journal of Clinical Oncology (2023)

616 Background: Accurate prediction of future glomerular function rate (fGFR) following nephrectomy in renal cell carcinoma (RCC) patients is of interest. A postoperative estimated glomerular filtration (eGFR) rate ≥ 45 mL/min/1.73m2 is considered favorable, with guidelines reflecting these findings. Though nephron sparing surgery is preferable, radical nephrectomy is often the preferred oncologic surgery. Various models to predict postoperative renal function have been proposed, with a new 2021 equation by Palacios et al. exhibiting strong performance in predicting fGFR. We aim to validate this fGFR equation in a large institutional cohort using both the Chronic Kidney Disease Epidemiology (CKD-EPI) 2009 equation with race, used in the creation of the formula, as well as the CKD-EPI 2021 equation without race, which is currently the recommended CKD-EPI creatinine equation. Methods: Using an institutional database, patients that underwent partial or radical nephrectomy for RCC from 2005-2021 were identified. Patients with creatinine values preoperatively and 3-12 months postoperatively were included, with end stage renal disease serving as exclusion criteria. Correlation/bias/accuracy/precision of the fGFR equation (fGFR=35+ [preoperative eGFR x 0.65]- 18 [if radical] - [age x 0.25]+ 3 [if tumor &gt;7cm]-2 [if diabetes]) with observed postoperative eGFR was determined by both the CKD-EPI-2021 and CKD-EPI 2009 equations. Results: 1,443 patients were included in our analysis. 71% (1,024) and 22.9% (331) patients were white and black, respectively. A majority of patients underwent radical nephrectomy (60.3%). 40% of patients had T3-T4 RCC, with 14.8% of patients having M1 disease. Median observed vs predicted fGFR was 58.0 vs 58.7 ml/min/1.73m2 for CKD-EPI 2021 and 56.0 vs 57.5 for CKD-EPI 2009. The correlation/bias/accuracy/precision of the fGFR equation was 0.805/-0.5/81.7/7.9-9.0 for CKD-EPI 2021 and 0.809/-0.8/81.3/-8.1-8 for CKD-EPI 2009 equations (Table). Conclusions: The fGFR equation accurately predicted renal function in our large and diverse institutional cohort using both the CKD-EPI 2009 including race and CKD-EPI 2021 excluding race equations. [Table: see text]